Non-invasive Trigeminal and Vagus Nerve Stimulation for Stroke Subjects With Chronic Upper Extremity Deficits

Feasibility of Trigeminal and Vagus Nerve Stimulation in Subjects With Chronic Upper Extremity Deficits After Stroke

This is a single-center, multiphase pilot study of 16 subjects with residual upper extremity deficits at least six months after a supratentorial ischemic or hemorrhagic stroke. The purpose of the study is to evaluate the clinical safety, device functionality, and treatment effect of non-invasive electrical stimulation of the trigeminal and/or vagus nerves (nTVNS) using the NeuraStasis Stimulator System adjunctive to rehabilitation. Phase 1 consisted of 5 unblinded subjects receiving nTVNS to assess device usability and safety. Phase 2 used a Prospective Randomized Open, Blinded Endpoint (PROBE) design comparing nTVNS to sham stimulation in 11 subjects. The study will inform the design and implementation of a pivotal study.

This pilot study proceeded in two phases: Phase I, an unblinded stage, and Phase II, a blinded stage comparing intervention and sham groups.

Phase I consisted of 5 subjects, unblinded, receiving nTVNS. This phase tested the usability of the device and de-risked the use of nTVNS during rehabilitation. Visits included consent and baseline evaluation, followed by 6 weeks of treatment consisting of upper extremity rehabilitation paired with nTVNS. Rehabilitation and treatment occurred at a cadence of 3 sessions per week. Primary endpoints was collected after 6 weeks.

Phase II consisted of a Prospective Randomized Open, Blinded Endpoint (PROBE) design with 11 subjects randomized to an intervention nTVNS group or a control sham stimulation group. Both groups received a stimulation tolerability assessment at the start of each session to support blinding for therapists and subjects. For the sham group, no stimulation was delivered during the priming or rehabilitation portions of the session. The same evaluations, sessions, and endpoints occurred as those in Phase 1.

Inclusion Criteria:

• History of unilateral supratentorial ischemic, intracerebral hemorrhagic, subarachnoid hemorrhagic, or a heterogeneous lesion stroke that occurred at least 6 months but not more than 15 years prior to enrollment.
• Age >30 years and <85 years.
• Fugl-Meyer Assessment, Upper Limb (FMA-UE) baseline score of 10 to 56 (inclusive of 10 and 56).
• Ability to communicate, understand, and provide appropriate consent. Subjects should be able to follow two-step commands.
• Right- or left-sided weakness of the upper extremity.

Exclusion Criteria

• Participant with any implanted metallic device at or near the stimulation sites (forehead and ears).

• Participant with an implanted or active stimulator (ex. Deep brain stimulator, pacemaker, vagus nerve stimulator, defibrillator)

• Participant skin in the stimulation area has open wounds, skin eruptions, swollen, infected, or inflamed areas, or skin abnormalities that could be cancerous

• Advanced cardiac, pulmonary, liver, kidney dysfunction or blood system disease

• Participant has a fever or shows clinical signs concerning for an infectious disease

• Other neurologic or musculoskeletal diseases that could interfere with the assessments of this study

• Low heart rate (<60 bpm) from a cardiac conduction block or related etiology

• Participant has a history of trigeminal neuralgia

• Participant has a history of Bell's Palsy

• History of cranial nerve neuropathy (including facial nerve injury), carotid surgery, vagotomy, or other surgical intervention on the vagus nerve

• History of recurrent syncopal events

• Known or newly-discovered aneurysm or arteriovenous malformation

• Patients who have any terminal illness such that the patient would not be expected to survive more than 90 days

• Botox injections 12 weeks prior to or during therapy

• Participants who have had a craniectomy:

  • Without replacement of bone flap
  • With bone flap replaced < 6 months prior to initiation of study activities